Parkinson's disease (shaking palsy) is a brain disease characterized by tremors (trembling or vibrating) of the body, as well as difficulties in walking, movements, and coordination.
The development of Parkinson's disease is related to a damage of a part of the brain which controls the muscular movements. Dopaminergic cells, which are concentrated in the relevant part of the substantia nigra, are the most rapidly aging cells in the body, and denaturation of dopamine-producing cells causes a reduction in the production of dopamine and impairs the control of movement, thus developing Parkinson's disease.
Symptoms very similar to Parkinson's disease as mentioned above are known to be also caused by various other causes, such as Encephalitis lethargica, cerebral arteriosclerosis, intoxication with drugs/carbon monoxide/manganese/cyanide compounds or the like, brain tumor, after a head injury, or syphilis. Including these, a condition in which symptoms such as muscle stiffness, tremor, or akinesia occur in different combinations is called “Parkinson's syndrome”.
No radical therapeutic methods are known for Parkinson's syndrome, and conventional therapeutic methods have been aimed at controlling the symptoms. Representative therapeutic methods include a method of administering to a patient L-DOPA, which is a precursor of dopamine, singly or in combination with another drug. However, when this therapeutic method is conducted for a long time period, the efficacy of L-DOPA tends to lower over time, and actually patients who received a chronic treatment with L-DOPA had a problem in that the aforementioned symptoms often became severe in addition to occurrence of other adverse reactions due to neurotoxicity intrinsic to L-DOPA.
On the other hand, adenosine is known to be an endogenous modulator of many physiological functions. It has been revealed that the action of adenosine is mediated by an interaction with different membrane specific receptors which belong to the family of G-protein coupled receptors present on the cell surface, and there are at least 4 subtypes of adenosine receptors, A1, A2a, A2b, and A3.
In recent years, the role of adenosine as a neurotransmitter, its receptors, and their functional properties have been discovered, and thereby it has been revealed that an antagonist of adenosine A2a receptor can be used as a therapeutic agent for movement disorder accompanied by Parkinson's syndrome (Patent Literatures 1 to 3).